scholarly journals Genetic Identification of Adenovirus Type 5 Genes That Influence Viral Spread

2006 ◽  
Vol 80 (4) ◽  
pp. 2000-2012 ◽  
Author(s):  
T. Subramanian ◽  
S. Vijayalingam ◽  
G. Chinnadurai
Keyword(s):  
Dna Sequences ◽  
Control Cell ◽  
Cancer Cell Line ◽  
Adenovirus Type ◽  
Viral Proteins ◽  
Genetic Identification ◽  
Large Plaque ◽  
Viral Spread ◽  
Leader Protein ◽  
Adenovirus Type 5

ABSTRACT The mechanisms that control cell-to-cell spread of human adenoviruses (Ad) are not well understood. Two early viral proteins, E1B-19K and E3-ADP, appear to have opposing effects since viral mutants that are individually deficient in E1B-19K produce large plaques (G. Chinnadurai, Cell 33:759-766, 1983), while mutants deficient in E3-ADP produce small plaques (A. E. Tollefson et al., J. Virol. 70:2296-2306, 1996) on infected cell monolayers. We have used a genetic strategy to identify different viral genes that influence adenovirus type 5 (Ad5) spread in an epithelial cancer cell line. An Ad5 mutant (dl327; lacking most of the E3 region) with the restricted-spread (small-plaque) phenotype was randomly mutagenized with UV, and 27 large-plaque (lp) mutants were isolated. A combination of analyses of viral proteins and genomic DNA sequences have indicated that 23 mutants contained lesions in the E1B region affecting either 19K or both 19K and 55K proteins. Four other lp mutants contained lesions in early regions E1A and E4, in the early L1 region that codes for the i-leader protein, and in late regions that code for the viral structural proteins, penton base, and fiber. Our results suggest that the requirement of E3-ADP for Ad spread could be readily compensated for by abrogation of the functions of E1B-19K and provide genetic evidence that these two viral proteins influence viral spread in opposing manners. In addition to E1B and E3 proteins, other early and late proteins that regulate viral replication and infectivity also influence lateral viral spread. Our studies have identified novel mutations that could be exploited in designing efficient oncolytic Ad vectors.

Sequence Analysis of the Putative E3 Region of Bovine Adenovirus Type 2

Intervirology ◽  
1994 ◽  
Vol 37 (5) ◽  
pp. 277-286
Author(s):  
L.E. Esford ◽  
Y. Haj-Ahmad
Keyword(s):  
Dna Sequences ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Open Reading Frames ◽  
Bovine Adenovirus ◽  
Adenovirus Type 5 ◽  
E3 Region ◽  
Adenovirus Type 2

Adenoviruses are nonenveloped icosahedral-shaped particles. The double-stranded viral DNA genome contains four major early transcription units, designated El (a and b), E2 (a and b), E3 and E4, which are expressed in a regulated manner soon after infection. The gene products of the region E3, shown to be nonessential for viral replication in vitro, are believed to be involved in counteracting host immunosurveillance. Human adenovirus type 5 DNA sequences of transcription units L4 and L5 adjacent to E3 were used to localize E3 within the bovine adenovirus type 2. The DNA sequences between 74.8 and 84.4 mu containing E3 and the fiber gene were determined. The E3 region was found to consist of about 2.3 kb pairs and to encode four proteins longer than 60 amino acids. However, these four open reading frames did not show significant homology to any other known adenovirus DNA or protein sequence.

Early viral proteins in HeLa cells infected with adenovirus type 5 host range mutants

Virology ◽  
1980 ◽  
Vol 103 (2) ◽  
pp. 475-492 ◽  
Author(s):  
Susan R. Ross ◽  
Arnold J. Levine ◽  
Richard S. Galos ◽  
Jim Williams ◽  
Thomas Shenk
Keyword(s):  
Host Range ◽  
Hela Cells ◽  
Adenovirus Type ◽  
Viral Proteins ◽  
Adenovirus Type 5

scholarly journals Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

2020 ◽  
Author(s):  
Rodney G King ◽  
Aaron Silva-Sanchez ◽  
Jessica N. Peel ◽  
Davide Botta ◽  
Selene Meza-Perez ◽  
...  
Keyword(s):  
Mucosal Immunity ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Adenovirus Type ◽  
First Line ◽  
Viral Spread ◽  
Cytokine Expression Profile ◽  
Preventive Vaccination ◽  
Vectored Vaccine ◽  
Adenovirus Type 5

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

scholarly journals Functional Interaction of the Adenovirus IVa2 Protein with Adenovirus Type 5 Packaging Sequences

2005 ◽  
Vol 79 (5) ◽  
pp. 2831-2838 ◽  
Author(s):  
Philomena Ostapchuk ◽  
Jihong Yang ◽  
Ece Auffarth ◽  
Patrick Hearing
Keyword(s):  
Specific Interaction ◽  
Point Mutations ◽  
Adenovirus Type ◽  
Viral Proteins ◽  
Dna Packaging ◽  
Sequence Motif ◽  
Site Specific ◽  
Adenovirus Type 5

ABSTRACT Adenovirus type 5 (Ad5) DNA packaging is initiated in a polar fashion from the left end of the genome. The packaging process is dependent on the cis-acting packaging domain located between nucleotides 230 and 380. Seven AT-rich repeats that direct packaging have been identified within this domain. A1, A2, A5, and A6 are the most important repeats functionally and share a bipartite sequence motif. Several lines of evidence suggest that there is a limiting trans-acting factor(s) that plays a role in packaging. Both cellular and viral proteins that interact with adenovirus packaging elements in vitro have been identified. In this study, we characterized a group of recombinant viruses that carry site-specific point mutations within a minimal packaging domain. The mutants were analyzed for growth properties in vivo and for the ability to bind cellular and viral proteins in vitro. Our results are consistent with a requirement of the viral IVa2 protein for DNA packaging via a direct interaction with packaging sequences. Our results also indicate that higher-order IVa2-containing complexes that form on adjacent packaging repeats in vitro are the complexes required for the packaging activity of these sites in vivo. Chromatin immunoprecipitation was used to study proteins that bind directly to the packaging sequences. These results demonstrate site-specific interaction of the viral IVa2 and L1 52/55K proteins with the Ad5 packaging domain in vivo. These results confirm and extend those previously reported and provide a framework on which to model the adenovirus assembly process.

Viral DNA Sequences in Cells Transformed by Simian Virus 40, Adenovirus Type 2 and Adenovirus Type 5

1974 ◽  
Vol 39 (0) ◽  
pp. 615-632 ◽  
Author(s):  
J. Sambrook ◽  
M. Botchan ◽  
P. Gallimore ◽  
B. Ozanne ◽  
U. Pettersson ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Simian Virus 40 ◽  
Adenovirus Type ◽  
Simian Virus ◽  
Viral Dna ◽  
Adenovirus Type 5 ◽  
Adenovirus Type 2 ◽  
In Cells

scholarly journals Multiple Vaccine-Elicited Nonneutralizing Antienvelope Antibody Activities Contribute to Protective Efficacy by Reducing both Acute and Chronic Viremia following Simian/Human Immunodeficiency Virus SHIV89.6P Challenge in Rhesus Macaques

2010 ◽  
Vol 84 (14) ◽  
pp. 7161-7173 ◽  
Author(s):  
Peng Xiao ◽  
Jun Zhao ◽  
L. Jean Patterson ◽  
Egidio Brocca-Cofano ◽  
David Venzon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Specific Activity ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Control Cell ◽  
Adenovirus Type ◽  
Secretory Iga ◽  
Viral Inhibition ◽  
Viral Spread ◽  
Immunodeficiency Virus

ABSTRACT We have shown that following priming with replicating adenovirus type 5 host range mutant (Ad5hr)-human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) recombinants, boosting with gp140 envelope protein enhances acute-phase protection against intravenous simian/human immunodeficiency virus (SHIV)89.6P challenge compared to results with priming and no boosting or boosting with an HIV polypeptide representing the CD4 binding site of gp120. We retrospectively analyzed antibodies in sera and rectal secretions from these same macaques, investigating the hypothesis that vaccine-elicited nonneutralizing antibodies contributed to the better protection. Compared to other immunized groups or controls, the gp140-boosted group exhibited significantly greater antibody activities mediating antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated viral inhibition (ADCVI) in sera and transcytosis inhibition in rectal secretions. ADCC and ADCVI activities were directly correlated with antibody avidity, suggesting the importance of antibody maturation for functionality. Both ADCVI and percent ADCC killing prechallenge were significantly correlated with reduced acute viremia. The latter, as well as postchallenge ADCVI and ADCC, was also significantly correlated with reduced chronic viremia. We have previously demonstrated induction by the prime/boost regimen of mucosal antibodies that inhibit transcytosis of SIV across an intact epithelial cell layer. Here, antibody in rectal secretions was significantly correlated with transcytosis inhibition. Importantly, the transcytosis specific activity (percent inhibition/total secretory IgA and IgG) was strongly correlated with reduced chronic viremia, suggesting that mucosal antibody may help control cell-to-cell viral spread during the course of infection. Overall, the replicating Ad5hr-HIV/SIV priming/gp140 protein boosting approach elicited strong systemic and mucosal antibodies with multiple functional activities associated with control of both acute and chronic viremia.

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